Enhancement of Folates in Plants through Metabolic Engineering

Humans depend on plants as a major source of dietary folates. Inadequate dietary levels of the vitamin folate can lead to megaloblastic anemia, birth defects, impaired cognitive development, and increased risk of cardiovascular disease and cancer. The biofortification of folate levels in food crops...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2004-04, Vol.101 (14), p.5158-5163
Main Authors: Hossain, Tahzeeba, Rosenberg, Irwin, Selhub, Jacob, Kishore, Ganesh, Beachy, Roger, Schubert, Karel
Format: Article
Language:English
Subjects:
Agricultural biotechnology
Arabidopsis - genetics
Arabidopsis - metabolism
Arabidopsis thaliana
Bacteria
Base Sequence
Biological Sciences
Biology
Biosynthesis
DNA
DNA Primers
Flowers & plants
Fluorescence
Folic Acid - metabolism
Gene expression
Genetic Engineering
Genetic vectors
Metabolism
Plants
Plants, Genetically Modified
Polymerase chain reaction
Proteins
Pterins
Transgenic plants
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Summary:Humans depend on plants as a major source of dietary folates. Inadequate dietary levels of the vitamin folate can lead to megaloblastic anemia, birth defects, impaired cognitive development, and increased risk of cardiovascular disease and cancer. The biofortification of folate levels in food crops is a target for metabolic engineering. Folates are synthesized de novo from pterins and para-amino benzoic acid, which are subsequently combined to form dihydropteroate, the direct precursor to dihydrofolate. We postulated that GTP cyclohydrolase-1, which catalyzes the first committed step in pterin biosynthesis, was a rate-limiting step in pterin synthesis in plants and, therefore, in folate synthesis. On this basis, we proposed that the expression of an unregulated bacterial GTP cyclohydrolase-1 in plants would increase pterin biosynthesis with a concomitant enhancement of folate levels. The folE gene encoding GTP cyclohydrolase-1 was cloned from Escherichia coli and introduced into Arabidopsis thaliana through plant transformation. The expression of bacterial GTP cyclohydrolase-1 in transgenic Arabidopsis resulted in a 1,250-fold and 2- to 4-fold enhancement of pterins and folates, respectively. These results helped to identify other potential factors regulating folate synthesis, suggesting ways to further enhance folate levels in food crops.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0401342101